SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT Fluconazol STADA** 50 mg capsule, hard Fluconazol STADA** 100 mg capsule, hard Fluconazol STADA** 150 mg capsule, hard Fluconazol STADA** 200 mg capsule, hard 2. QUALITATIVE AND QUANTITATIVE COMPOSITION One hard capsule contains 50 / 100 / 150 / 200 mg fluconazole Excipient with known effect Each capsule, hard contains 41 / 82 / 123 / 164 mg of lactose monohydrate. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Capsule, hard Fluconazol STADA 50 mg hard capsules are pale blue/white Fluconazol STADA 100 mg hard capsules are light blue/white Fluconazol STADA 150 mg hard capsules are white Fluconazol STADA 200 mg hard capsules are blue/white 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Fluconazole is indicated in the following fungal infections (see section 5.1): Fluconazole is indicated in adults for the treatment of: Cryptococcal meningitis (see section 4.4). Coccidioidomycosis (see section 4.4). Invasive candidiasis. Mucosal candidiasis including oropharyngeal, oesophageal candidiasis, candiduria and chronic mucocutaneous candidiasis. Chronic oral atrophic candidiasis (denture sore mouth) if dental hygiene or topical treatment are insufficient. Vaginal candidiasis, acute or recurrent; when local therapy is not appropriate. Candidal balanitis when local therapy is not appropriate. Dermatomycosis including tinea pedis, tinea corporis, tinea cruris, tinea versicolor and dermal candida infections when systemic therapy is indicated. Tinea unguinium (onychomycosis) when other agents are not considered appropriate. Fluconazole is indicated in adults for the prophylaxis of: ** working title used during MRP ** working title used during MRP ** working title used during MRP ** working title used during MRP Relapse of cryptococcal meningitis in patients with high risk of recurrence. Relapse of oropharyngeal or oesophageal candidiasis in patients infected with HIV who are at high risk of experiencing relapse. To reduce the incidence of recurrent vaginal candidiasis (4 or more episodes a year). Prophylaxis of candidal infections in patients with prolonged neutropenia (such as patients with haematological malignancies receiving chemotherapy or patients receiving Hematopoietic Stem Cell Transplantation (see section 5.1)). Fluconazole is indicated in term newborn infants, infants, toddlers, children, and adolescents aged from 0 to 17 years old: Fluconazole is used for the treatment of mucosal candidiasis (oropharyngeal, oesophageal), invasive candidiasis, cryptococcal meningitis and the prophylaxis of candidal infections in immunocompromised patients. Fluconazole can be used as maintenance therapy to prevent relapse of cryptococcal meningitis in children with high risk of reoccurrence (see section 4.4). Therapy may be instituted before the results of the cultures and other laboratory studies are known; however, once these results become available, anti-infective therapy should be adjusted accordingly. Consideration should be given to official guidance on the appropriate use of antifungals. 4.2 Posology and method of administration Posology The dose should be based on the nature and severity of the fungal infection. Treatment of infections requiring multiple dosing should be continued until clinical parameters or laboratory tests indicate that active fungal infection has subsided. An inadequate period of treatment may lead to recurrence of active infection. Adults Indications Posology Duration of treatment Cryptococcosis - Treatment of Loading dose: Usually at least 6 to cryptococcal 400 mg on Day 1 8 weeks. meningitis. Subsequent dose: In life threatening 200 mg to 400 mg infections the daily daily dose can be increased to 800 mg - Maintenance 200 mg daily Indefinitely at a daily therapy to prevent dose of 200 mg relapse of cryptococcal meningitis in patients with high risk of recurrence. Coccidioidomycosis 200 mg to 400 mg 11 months up to 24 months or longer depending on the patient. 800 mg daily may be considered for some infections and especially for meningeal disease Invasive candidiasis Loading dose: In general, the 800 mg on Day 1 recommended Indications Posology Duration of treatment Subsequent dose: duration of therapy 400 mg daily for candidaemia is for 2 weeks after first negative blood culture result and resolution of signs and symptoms attributable to candidaemia. Treatment of - Oropharyngeal Loading dose: 7 to 21 days (until mucosal candidiasis 200 mg to 400 mg oropharyngeal candidiasis on Day 1 candidiasis is in Subsequent dose: remission). 100 mg to 200 mg Longer periods may daily be used in patients with severely compromised immune function - Oesophageal Loading dose: 14 to 30 days (until candidiasis 200 mg to 400 mg oesophageal on Day 1 candidiasis is in Subsequent dose: remission). 100 mg to 200 mg Longer periods may daily be used in patients with severely compromised immune function - Candiduria 200 mg to 400 mg 7 to 21 days. Longer daily periods may be used in patients with severely compromised immune function. - Chronic atrophic 50 mg daily 14 days candidiasis - Chronic 50 mg to 100 mg Up to 28 days. mucocutaneous daily Longer periods candidiasis depending on both the severity of infection or underlying immune compromisation and infection Prevention of - Oropharyngeal 100 mg to 200 mg An indefinite period relapse of mucosal candidiasis daily or 200 mg 3 for patients with candidiasis in times per week chronic immune patients infected suppression with HIV who are at - Oesophageal 100 mg to 200 mg An indefinite period high risk of candidiasis daily or 200 mg 3 for patients with experiencing times per week chronic immune relapse suppression Genital candidiasis - Acute vaginal 150 mg Single dose candidiasis - Candidal balanitis Indications Posology Duration of treatment - Treatment and 150 mg every third Maintenance dose: prophylaxis of day for a total of 3 6 months. recurrent vaginal doses (day 1, 4, and candidiasis (4 or 7) followed by more episodes a 150 mg once weekly year). maintenance dose Dermatomycosis - tinea pedis, 150 mg once weekly 2 to 4 weeks, tinea - tinea corporis, or 50 mg once daily pedis may require - tinea cruris, treatment for up to - candida infections 6 weeks - tinea versicolor 300 mg to 400 mg 1 to 3 weeks once weekly 50 mg once daily 2 to 4 weeks - tinea unguium 150 mg once weekly Treatment should be (onychomycosis) continued until infected nail is replaced (uninfected nail grows in). Regrowth of fingernails and toenails normally requires 3 to 6 months and 6 to 12 months, respectively. However, growth rates may vary widely in individuals, and by age. After successful treatment of long-term chronic infections, nails occasionally remain disfigured. Prophylaxis of 200 mg to 400 mg Treatment should candidal infections start several days in patients with before the prolonged anticipated onset of neutropenia neutropenia and continue for 7 days after recovery from neutropenia after the neutrophil count rises above 1000 cells per mm3. Special populations Elderly Dosage should be adjusted based on the renal function (see “Renal impairment”). Renal impairment No adjustments in single dose therapy are necessary. In patients (including paediatric population) with impaired renal function who will receive multiple doses of fluconazole, an initial dose of 50 mg to 400 mg should be given, based on the recommended daily dose for the indication. After this initial loading dose, the daily dose (according to indication) should be based on the following table: Creatinine clearance (ml/min) Percent of recommended dose > 50 100 % ≤ 50 (no dialysis) 50 % Regular dialysis 100 % after each dialysis Patients on regular dialysis should receive 100 % of the recommended dose after each dialysis; on non-dialysis days, patients should receive a reduced dose according to their creatinine clearance. Hepatic impairment Limited data are available in patients with hepatic impairment, therefore fluconazole should be administered with caution to patients with liver dysfunction (see sections 4.4 and 4.8). Paediatric population A maximum dose of 400 mg daily should not be exceeded in paediatric population. As with similar infections in adults, the duration of treatment is based on the clinical and mycological response. Fluconazole is administered as a single daily dose. For paediatric patients with impaired renal function, see dosing in “Renal impairment”. The pharmacokinetics of fluconazole has not been studied in paediatric population with renal insufficiency (for “Term newborn infants” who often exhibit primarily renal immaturity please see below). Infants, toddlers and children (from 28 days to 11 years old): Indication Posology Recommendations - Mucosal candidiasis Initial dose: 6 mg/kg Initial dose may be used on Subsequent dose: 3 mg/kg the first day to achieve daily steady state levels more rapidly - Invasive candidiasis Dose: 6 to 12 mg/kg daily Depending on the severity of - Cryptococcal meningitis the disease - Maintenance therapy to Dose: 6 mg/kg daily Depending on the severity of prevent relapse of the disease cryptococcal meningitis in children with high risk of recurrence - Prophylaxis of Candida in Dose: 3 to 12 mg/kg daily Depending on the extent immunocompromised and duration of the induced patients neutropenia (see Adults posology) Adolescents (from 12 to 17 years old): Depending on the weight and pubertal development, the prescriber would need to assess which posology (adults or children) is the most appropriate.